Study of 4 major aspects of adrenocortical system function will be initiated or continued in this application: 1) Non-steroidal adrenal feedback that modulates stimulus-induced CRF and ACTH secretion will be studied by manipulating adrenal mass using ACTH with or without steroid synthesis inhibitors. To test whether the non-steroidal signal is mediated neurally or humorally, we will study the effects of increased adrenal mass in rats with CNS lesions or with transplanted adrenals. 2) Adrenal regeneration after bilateral adrenal enucleation will be studied to test the hypothesis that regeneration is regulated by increases in circulating levels of Angiotensin II and ACTH. 3) Pituitary factors that augment adrenal responsiveness to ACTH will be studied using parallel in vivo and in vitro systems in an attempt to document the existence of such factors and to delineate the conditions under which they are secreted. 4) Stimulus-response relationships will be determined in conscious dogs and rats for the stimuli of hypoglycemia hypoxia. The responses determined will include plasma ACTH, corticosteroids, vasopressin and epinephrine. Effective stimulus characteristics will be determined for both stimuli, and we will also study adaptation to low rates of change in the stimuli, and hormonal off responses. The effects of prior administration of ACTH or corticosteroid infusions on subsequent endocrine responses will be determined.